TUMOR-INDUCED OSTEOMALACIA (TIO) a Resource Guide for Patients and Care Partners

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TUMOR-INDUCED OSTEOMALACIA (TIO) A Resource Guide for Patients and Care Partners

This information is for educational purposes only and is not intended to provide medical advice. Your healthcare professional should always be your primary source of medical advice for any health, diagnosis, or management practices. WHAT IS TIO?

TIO, or tumor-induced osteomalacia, is an ultra-rare disease caused by small tumors that produce too much of a protein called fibroblast growth factor 23 (FGF23).

Increased levels of FGF23 lead to the loss of phosphate through the kidneys and urine – a process called phosphate wasting.

This causes hypophosphatemia, or a lower-than-normal amount of phosphorus in the blood, which also results in a lower amount of phosphorus in the bones – a condition called osteomalacia.1-3

TIO is acquired, which means you are not born with it. Doctors may call TIO by other names, such as: • Oncogenic osteomalacia • Oncogenic hypophosphatemic osteomalacia

Common Symptoms

The symptoms of TIO result from the low amounts of phosphorus in the blood and bones, rather than from the tumor itself.4 People with TIO typically experience:1,3-8 • Fatigue/general weakness (muscle weakness and loss of muscle mass) • Weak bones that break or fracture easily • Severe muscle and bone pain, which can get worse over time • Mobility issues, including difficulty walking and possible need for a wheelchair

“If the pain wasn’t there, I could function, but TIO prevents me from doing a lot of things.” — Jason, age 44, living with TIO

2 UltraRareAdvocacy.com TIO Tumors Diagnosis

TIO tumors can be as small as 1 cm (the size of The journey to diagnosis can be long and a pea) and may be difficult or impossible to find. challenging. TIO is commonly misdiagnosed, The cause of tumors that lead to TIO is unknown. sometimes as a musculoskeletal or rheumatologic They can occur anywhere in the body, but most disease11,12, or as stress-related symptoms. often occur in the legs and feet.9,10

It can take as long as 2.5 to 28 years to get a definitive diagnosis of TIO.1,13

“It was a relief to get the words of the diagnosis, and it launched me into the next stage: research.” — Lenora, age 54, living with TIO

During their search for a diagnosis, people may undergo many tests, including: 1,14 • Blood tests • Urine tests • Positron emission tomography (PET) scans • Computed tomography (CT) scans • X-rays • Dual energy X-ray absorptiometry (DEXA) scans (to assess bone density) • Magnetic resonance imaging (MRI)

Blood and/or urine tests that measure levels of phosphorus, vitamin D, FGF23, parathyroid hormone, and liver enzymes may point to a diagnosis of TIO. Patients may also undergo assessments of phosphate reabsorption and kidney function.1,2 Functional body scans and imaging are performed to try to locate tumors in individuals with suspected TIO.1,14 In deciding which scanning or imaging technique to use, healthcare professionals will consider factors such as the suspected location of the tumor and the technique that can offer the best image.

3 UltraRareAdvocacy.com HOW DO I MANAGE TIO?

The symptoms of TIO make it a complex disease that often involves afocused care and management plan, including assistance with everyday tasks and mobility. That makes it especially important for people to advocate for their own needs and to have support from family and friends to help them navigate the healthcare system.

If the tumor(s) can be located, the next step may be surgery to remove the tumor(s). This may be curative for TIO, as it leads to a rapid decrease in FGF23 levels and balances out the amount of phosphate in the body, which results in relief of symptoms.

Surgery is not always able to remove the entire tumor, and in some cases the tumor may reappear or there may be multiple tumors. Additionally, if the tumor cannot be identified or operated on, the person may instead need to manage their condition with medications.1

Addressing Your Mental Health

Living with a rare condition can feel overwhelming, which is why it is important to pay attention to your mental health. Here are some tools that may help:

Self-care Try to find time for something you enjoy doing, or something new. Be alert to the signs of depression, such as feeling sad, anxious, or “empty,” having difficulty concentrating or sleeping, feeling restless and/or irritable, or feeling hopeless.15 These feelings are common and normal, but if they interfere with your daily activities, consider talking to your TIO specialist or primary care doctor, who may refer you to a mental health professional.

Coping techniques There are a number of techniques you can use on your own or with a therapist to help manage stress and anxiety. • Some of these are emotion-focused strategies, which can be used in situations that you cannot (or don’t want to) change.16 These include breathing exercises, meditation, visualization strategies, and relaxing activities such as spending time with your pet, crafting, light exercise, or connecting with friends. • Others are solution-focused strategies, which are used in situations you can change, or change the way you handle them.16 These include listening to podcasts or audiobooks, consulting with an occupational therapist about tools you can use to make your home, workplace, or car more usable or comfortable, and talking to your teacher or boss about any negative feedback you may receive about your work or performance.

4 UltraRareAdvocacy.com Peer support You may find comfort and support from connecting with others who share your experience. This can be done in person, over the phone, or online through social media channels and email. See the Resources section of this brochure for a list of advocacy groups and forums that offer peer support.

Managing Appointments

Your challenges, goals, and questions will change over time, so stay organized! There are tools included in this booklet to help you make the most of your doctor visits. • Keep track of and prepare for medical appointments using the Doctor Discussion Guide (page 9) • Bring someone with you to help you take notes or remember details • Keep copies of your medical records and use the Medical History Template (page 7) • Provide copies to your healthcare team whenever possible, especially if you change doctors or see a new doctor you haven’t met with before

“You’re in the midst of a massive crisis, so you need to forgive yourself for whatever you do or don’t do wrong because you’re trying to juggle things that are just inexplicable, but there’s also a little bit of assertiveness required, which is asking those tough questions to make sure that you get the answers and the advocacy that you need.” — Ann, age 50, living with TIO

TIO:5 Tumor-Induced Osteomalacia 5 Home Modifications

Managing daily life while living with TIO may require making some changes within your home. Here are a few simple and cost-effective things you can do to make your daily life easier: • Place handrails in key areas, such as near the toilet and shower/bath, and alongside the bed • Add grips to the floor of the shower/bath • Place non-slip materials on tile floors • Store pots, pans, and utensils in places that don’t require bending • Ensure flooring is level (and not too slippery or too rough to move wheels on) • Spread out furniture in key common areas such as the kitchen or living room • Leave a spare key with a trusted friend or neighbor in case of emergencies

For additional tips on home accommodations, see The Mighty’s list of Smart Home devices for people with disabilities at themighty.com/2017/08/smart-home-devices-for-people-with-disabilities.

Plan Ahead!

It’s common for someone with limited mobility to need more time and a plan to get ready for an event, for school or work, or just to go run errands. Keep an organized schedule with extra time built in. Be realistic – don’t overbook or choose something that may be too physically strenuous. There are a number of small but important steps you can take: • Check for accessible parking beforehand • If there’s walking involved, assess the distance you may be required to walk • Check for accessibility features wherever you’re going

The following tips can be helpful in planning for emergencies: • Familiarize yourself with your current life, property, and health insurance policies • Learn how to safely turn off water, natural gas, and electricity in your home • Build an emergency kit containing things you use on a daily basis, including medications. For a list of additional items, visit ready.gov/kit

To learn more about emergency planning for individuals with disabilities, visit ultrarareadvocacy.com/rare-prepared- emergency-planning-for-individuals-with- complex-healthcare-needs.

6 UltraRareAdvocacy.com MEDICAL HISTORY TEMPLATE Disease and Journey Overview

Provide information about your journey living with TIO, including when you were diagnosed, any misdiagnoses, and key medical events since your diagnosis. Also note your current health goals and anything else that might be useful for your healthcare team to know about your disease and experiences.

Emergency Contact

Name Relationship Phone

Allergies or Food Sensitivities

Healthcare Provider Contact Information

Primary TIO Healthcare Provider(s) (the person responsible for your day-to-day TIO management)

Name Institution Phone Email Frequency of Visits

Additional Healthcare Providers (including physical therapist [PT], occupational therapist [OT])

Name Institution Phone Email Frequency of Visits

7 UltraRareAdvocacy.com Current and Past Medications

Medication / Supplement Dose Frequency Current or Past?

Past Surgeries/Procedures

Date Surgery or Procedure Hospital or Clinic Name

Location(s) of Tumor(s)

Location / Body Part Tumor Type Current or Past?

Lab Results

Date of Measurement Phosphorus Level (mg/dL or mmol/L) FGF23 Levels (mg/dL or mmol/L)

8 UltraRareAdvocacy.com TALKING TO YOUR DOCTOR ABOUT TIO

Talking to your doctor isn’t always easy. You may not have a lot of time during the appointment, and it can be hard to explain exactly what’s wrong. Filling out this Doctor Discussion Guide prior to your appointment can help you get the most from your doctor visits. It is designed to help you start the conversation about symptoms, challenges, questions, and concerns you may face. My TIO Experience

I am experiencing the following symptoms: Mark on diagram where symptoms occur: (check all that apply) Bone pain Muscle pain Pain in a specific area or body part(s):

I have pain, but I’m not sure what kind Limited range of motion General muscle weakness Muscle weakness in a specific area:

Fatigue/exhaustion Difficulty walking My pain is typically worse: (check one) Mornings I experience pain: (check one) Mid-day Most of the day Evenings Some of the day During sleep During activities It lasts all day

How would you rate your worst pain level recently? Below is a typical pain scale doctors may use.

0 1 2 3 4 5 6 7 8 9 10 No pain Very mild Minor Noticeable Strong Piercing Intense Very Horrible Excruciating Unimaginable intense

Pain can be difficult to explain. It might be helpful to ask your doctor for a referral to a pain specialist.

9 UltraRareAdvocacy.com Some of these symptoms are new or have recently changed: (please explain)

When I walk, I find myself needing support, or assistive equipment: (check one) Not at all Sometimes Most of the time All of the time

For walking support, I typically use (e.g., a cane, crutches, the wall, hand rail):

I’m struggling with: (check all that apply) I am concerned about: (check all that apply) Performing daily activities Getting older Walking up and down stairs The progression of my disease Sleeping Working vs. disability Exercising Starting a relationship Feeling depressed Getting health insurance Feeling anxious What my health insurance covers Other: How to find a specialist Other:

I would like more help with, or information about:

When I think about my future health, I am most concerned about:

Action Plan My doctor and I decided on these next steps:

My next appointment is on at . (date) (time)

10 UltraRareAdvocacy.com Focus on Care Partner Health Messages of Support: A Care

It is just as important for care partners to take care Partner’s Story of themselves as it is to take care of the person with Mary has been caring for her sister Margaret for TIO. Helping someone manage TIO can be hard. the last decade, and has had a front-row seat to According to research by the National Alliance for Margaret’s long journey living with TIO. From the Caregiving, nearly 4 in 10 care partners consider first signs of mysterious hip pain, to visits to several their situation to be highly stressful, and 28% of doctors who found “nothing wrong,” to finally survey respondents reported moderate emotional receiving a TIO diagnosis, Mary has been a constant stress.17 Take some time for yourself to recharge, source of support to her sister. But it hasn’t de-stress, and restore your energy. It may help to: been easy.

Connect with other care partners of people with “It’s very hard when you don’t know what’s going rare or chronic illnesses online or on social media on and there’s nobody that could answer questions – even the doctor who figured it out – because Incorporate a stress-reducing activity like so few people have this condition,” Mary recalls. exercise, meditation, yoga, or walking into your “It just helps when you know what to expect and daily or weekly routine what’s going on.”

Keep up healthy habits like getting enough sleep, Mary discovered that caring for someone with TIO regular health checkups, and eating well to feel well involved more than cooking, cleaning, taking her sister to appointments, and helping her get in and out of the house. One of Mary’s biggest challenges Sample Checklist was coping with the emotional ramifications of the for Care Partners disease, and it pained her to see how TIO changed Margaret’s path in life. “It affected [Margaret] so Care partners may appreciate having a checklist much she could no longer practice her calling, of things they can do to help you manage your helping children with psychological problems. She TIO, while also keeping themselves physically and didn’t follow the path she thought she was going mentally healthy. This might include things like: to follow,” Mary comments. “I know she would be ❒ Medication schedule down and have really bad days. She would talk about it and I could see she was depressed.” ❒ Warning signs/symptoms to watch out for and what to do when they occur But the emotional impact of TIO was not limited ❒ Other areas of concern (e.g., daily to her sister. “It’s just difficult for everybody,” Mary activities, sleeping, exercise, depression) says. “You lose a lot of energy, so you just need to ❒ Storage of key documents (e.g., medical go day to day.” records, passports, birth certificates) Mary’s experience caring for Margaret has given ❒ Key phone numbers (family, doctors, her some valuable insights for fellow care partners. nearby hospitals) “Whatever [your loved one’s] needs are, they might not be able to get up and do it themselves,” she advises. “They’re really going to need you as the condition progresses. Get all the tools you can to make living as easy as possible.” 11 UltraRareAdvocacy.com RESOURCES You are not alone. Patient support and advocacy organizations provide useful information and resources for people and families living with TIO.

The XLH Network, Inc. is a US-based, nonprofit organization that has been serving the X-linked hypophosphatemia (XLH) and TIO patient communities for more than 20 years. Members have access to a variety of tools that help them connect with each other, with clinicians, and with researchers. xlhnetwork.org

National Organization for Rare Disorders (NORD) is an organization committed to the identification, treatment, and cure of rare disorders through programs of education, advocacy, research, and patient services. rarediseases.org

Global Genes is a rare disease patient advocacy organization that works to build awareness, educate the global community, and provide connections and resources. globalgenes.org

NIH Genetic and Rare Diseases (GARD) Information Center provides access to current, reliable, and easy-to-understand information about rare or genetic diseases. rarediseases.info.nih.gov

The Ultragenyx Patient Advocacy team is passionate about educating and supporting patients, families, and care partners affected by rare and ultra-rare genetic diseases. The Ultragenyx Patient Advocacy website offers access to disease information, education and support resources, an events calendar, and stories from patients about their personal journeys. ultrarareadvocacy.com REFERENCES

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